This competitive renewal application for a training grant requests funds for 9 predoctoral and 9 postdoctoral trainees. The goal is to provide opportunities for research training on molecular genetics approaches to biology and pathology of aging, with special emphasis upon a variety of model organisms and cell cultures that are amenable to genetic analysis (S. cerevisiae, C. elegans, M. domesticus, H. sapiens); such materials should permit trainees to address fundamentaI mechanisms highly relevant to aging and age-related diseases, including Alzheimer's disease (AD) and cancer. Didactic experiences will include courses in biochemistry, genetics, cell biology and pathology, research seminars, journal clubs, reviews of on-going research (approximately 60 individual and 6 program-projects, LEAD or center grants in aging), and a course on "Molecular Genetic Approaches to Aging," and bi-monthly "Aging Journal Club." In addition, trainees will typically participate in weekly lab meetings and in individual conferences with their mentors. Research projects will include efforts to identify genes related to various forms of familial and sporadic AD, delineations of mechanisms of p -amyloidogenesis and of its suppression, the role of the Wemer syndrome helicase gene in aging and cancer, studies of free radical injury and defense in relation to aging, DNA damage and mutation in aging, and mechanisms underlying the limited replicative potential of somatic cells. [unreadable] [unreadable]